We measured CT images instead of USG images in our study for several reasons. Brain CT is performed especially for patients with severe head trauma to evaluate for possible hematoma and fracture and the need for emergency surgery. ONSD can also be measured objectively on brain CT performed as indicated, and USG measurement of ONSD may not be needed. Ultrasonographic measurements are dependent on the practitioner, require experience, and can provide subjective results.
Helmke and Hansen [13] reported that the maximum enlargement of the ONSD was 3 mm from the optic nerve head in patients with increased intracranial pressure. In most studies, measurements were based on this distance. However, the location and distance to the eyeball of the optic nerve also change because of eye movements [29]. Thus, we thought that it would be appropriate to measure ONSD at two different distances, 3 and 8–12 mm from the bulbus oculi, as the children included in our study were less likely able to keep their eyes fixed during imaging. We used a second measurement site because studies have reported that measurements at 8–10 mm might be more reliable [28, 29]. The length of the intraorbital optic nerve usually range from 15 to 24 mm, and the middle ONSD measurement site in our study was the middle part of the intraorbital optic nerve [29].
We know that measurement is affected by many factors other than eye movements [29]. Therefore, we carefully selected the patients included in our study, with preference for those who did not have any problems that could affect intracranial pressure and the eyeball; whose height, weight, and head circumference were in the appropriate ranges; and whose neurodevelopment was normal (Supplementary Tables 1 and 2). We considered it appropriate to exclude racial/ethnic differences to reduce diversity and ensure standardization, so we included only Turkish patients. The meta-analysis revealed that apart from all these factors, the altitude of the place where the measurement was made and the individual patient characteristics also affected the ONSD measurement values. A previous study reported that the ONSD measurement increased by 0.14 mm for every 1000-m increase in altitude [35]. The hospital where our study was conducted and the CT images were obtained is located at an altitude of 8 m (26 ft). For this reason, we think that the normal median values we obtained are the smallest values, and it is important to keep this detail in mind when measuring at high altitudes.
Several studies have investigated normal ONSD values in healthy children [16–18, 23–27]. Most of these studies used USG for the measurements [16–18, 24, 27] and evaluated mostly patients in a control group [16–18, 26, 27]. Normal ONSD values obtained using USG range from 1.9 to 3.5 mm for ages ≤4 years and between 2.2 and 4 mm for ages > 4 years [16–18, 27]. Unlike other studies, the study by Steinborn et al. [23] showed that the normal ONSD value was 5.75 mm in 99 healthy children. While the cutoff ONSD measurement value for predicting increased intracranial pressure was reported to be 4.5 mm in some studies [17–19, 22], this value was reported as normal in another study [23]. Similarly to our study, two studies investigated normal ONSD values on CT. Gupta et al. [25] reported that the mean ONSD value was 4.78 mm in people aged 7–71 years. In the study by Kayadibi et al. [9], the mean ONSD values were 3.25 mm for ages 0–3 years, 3.60 mm for ages 3–6 years, 3.80 mm for ages 6–12 years, and 3.85 mm for ages 12–18 years. In our study, the proximal ONSD values ranged from 4.89 to 5.33 mm in the youngest age group (1 month to 2 years old) and from 5.75 to 5.80 mm in the oldest age group (10–18 years old). The results we obtained are similar to those of the study by Steinborn et al. [23]. However, their study was conducted with 99 healthy children with a mean age of 12 years and did not discriminate for sex [23].
In our study, statistically significant differences in ONSD and ETD values were found between the age groups. However, in the multiple comparisons, no statistically significant differences in all parameters were found between the 4- to 10-year-old and 10- to 18-year-old age groups. These results suggest that no significant changes in ONSD and ETD values occur from ages 4 to 18 years. Similar to our results, the ONSD values did not significantly change after the age of 4 years in another study (24). Contrary to these results, no significant changes were found after the age of 6 and 10 years in other studies [9, 26, 36]. However, studies have also reported that ONSD values increase with age even in the adult age group [37, 38].
In recent years, to resolve the dilemma arising from the variability of normal ONSD values, studies have investigated the ONSD/ETD ratio to create a constant value by proportioning the ONSD value to other measurements that vary with age [28–32]. While the ONSD and ETD values we determined in our study differed significantly between the age groups, the ONSD/ETD ratio did not differ significantly between the age groups. This is one of our important findings that support that this ratio can be used in all age groups. Vaiman et al. [29] investigated ONSD measurements and ONSD/ETD ratios using brain CT in 400 healthy adults and found that the ONSD/ETD index for healthy adults is 0.19. Calculations were made from measurements made at 10 mm from the eyeball. In our study, the ONSD middle/ETD ratio (0.19–0.20) was similar to the value obtained in the previous study. Bartsikhovsky et al. [32] reported that an ONSD/ETD ratio of > 0.21 on brain CT in pediatric patients could predict patients with headache and papilledema with 82% sensitivity and 93% specificity. In the same study, 94 patients with a mean age of 11 years were specified as the control group, and their median ONSD/ETD ratio was 0.17. In the present study, ONSD was measured from the area where the ophthalmic vein crosses the optic nerve, and the middle ONSD approximately corresponds to the area where we made the measurement. In our study, the middle ONSD/ETD ratio (0.19–0.20) was higher than that obtained by Bartsikhovsky et al. [32].
Our study is the first to determine normal ONSD and ONSD/ETD values using brain CT in a completely healthy pediatric age group according to age and sex. When the parameters were evaluated according to sex, the ONSD and ETD values were found to be statistically significantly higher in the boys than in the girls. On the other hand, the ONSD/ETD ratio did not show a significant difference according to sex. A previous study conducted in the adult age group also supports our results [38].
We conducted this study because ONSD measurement is a method that correlates with intracranial pressure [3, 7–11]. However, Biggs et al. [39] recently reported that ultrasonographic ONSD measurement did not correlate with increased intracranial pressure in patients followed up in the pediatric intensive care unit. However, considering the variability of normal ONSD and ONSD/ETD values, future studies with more patients and diseases are needed to obtain a series of measurement values, not as a single measurement, to investigate whether measurement values change according to clinical situation.